Dual function prosthetic bone implant and method for preparing the same

ABSTRACT

The present invention discloses a prosthetic bone implant made of a hardened calcium phosphate cement having an apatitic phase as a major phase, which includes a dense cortical portion bearing the majority of load and a porous cancellous portion allowing a rapid blood/body fluid penetration and tissue ingrowth.

PRIORITY CLAIM

This application is a continuation of and claims priority toNon-Provisional Patent Application No. 10/852,167 entitled “DUALFUNCTION PROSTHETIC BONE IMPLANT AND METHOD FOR PREPARING THE SAME”filed on May 25, 2004 now U.S. Pat. No. 6,994,726.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is related to a prosthetic bone implant made of ahardened calcium phosphate cement having an apatitic phase as a majorphase, and in particular to a prosthetic bone implant comprising a densecortical portion bearing the majority of load and a porous cancellousportion allowing a rapid blood/body fluid penetration and tissueingrowth.

2. Description of the Related Art

It is advantageous if a prosthetic bone implant is bioresorbable and issupportive at the same time. Accordingly, an article made of calciumphosphate will be preferable than that made of a metal, if the formerhas strength which is comparable to a human cortical bone. One way ofmaking such a bone implant is by sintering a calcium phosphate powder,particularly a hydroxyapatite (HA) powder, into a block material at atemperature generally greater than 1000° C. Despite the fact that thehigh temperature-sintered HA block material has an enhanced strength,the bioresorbability of the material is largely sacrificed, if nottotally destroyed, due to the elimination of the micro- and nano-sizedporosity during the sintering process.

The conventional spinal fusing device is composed of a metallic cage anda bioresorbable material disposed in the metal cage, for example the onedisclosed in U.S. Pat. No. 5,645,598. An inevitable disadvantage of thisfusion device is the sinking of the metallic cage sitting between twovertebrae to replace or repair a defect spinal disk, because thehardness and the relatively small size of the cage wear out or break thebone tissue, and in particular the endplate of the vertebra.

SUMMARY OF THE INVENTION

A primary objective of the invention is to provide a prosthetic boneimplant free of the drawbacks of the prior art.

The prosthetic bone implant constructed according to the presentinvention is made of a hardened calcium phosphate cement having anapatitic phase as a major phase, which comprises a dense corticalportion bearing the majority of load and a porous cancellous portionallowing a rapid blood/body fluid penetration and tissue ingrowth.

The prosthetic bone implant of the present invention is made by a noveltechnique, which involves immersing an article molded from two differentpastes of calcium phosphate cement (CPC), one of them having anadditional pore-forming powder, in a liquid for a period of time, sothat the compressive strength of the molded CPC article is significantlyimproved after removing from the liquid while the pore-forming powder isdissolved in the liquid, creating pores in a desired zone or zones ofthe molded article.

Features and advantages of the present invention are as follows:

1. Easy process for different shape and size of the prosthetic boneimplant of the present invention, so that the outer circumferentialdense portion thereof can sit over the circumferential cortical portionof a bone and the porous portion thereof can contact the cancellousportion of the bone adjacent to a bone receiving treatment.

2. The dense cortical portion of the prosthetic bone implant madeaccording to the present invention exhibits a high strength comparableto that of human cortical bone (about 110–170 MPa). The strength isadjustable by adjusting process parameters.

3. The dense cortical portion of the prosthetic bone implant madeaccording to the present invention contains significant amount of micro-and nano-sized porosity, that improves bioresorbability thereof.Conventional high temperature-sintered HA block, on the other hand, doesnot possess sufficient micro/nano-sized porosity and is notbioresorbable.

4. The porous cancellous portion of the prosthetic bone implant madeaccording to the present invention possesses a porosity greater than 40%in volume, prepferably 40–90%, allowing rapid blood/body fluidpenetration and tissue ingrowth, thereby anchoring the prosthetic boneimplant.

5. A wide range of medical application includes bone dowel, spacer,cavity filler, artificial disc and fixation devices for spine and otherlocations, to name a few.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 a to 1 d show schematic cross sectional views of four differentdesigns of prosthetic bone implants constructed according to the presentinvention.

FIGS. 2 a to 2 f are schematic cross sectional views showing steps of amethod for preparing a prosthetic bone implant according to oneembodiment of the present invention.

FIGS. 3 a and 3 b are schematic vertical and horizontal cross sectionalviews of a prosthetic bone implant prepared according to anotherembodiment of the present invention, respectively.

DETAILED DESCRIPTION OF THE INVENTION

Preferred embodiments of the present invention includes (but not limitedto) the following:

-   1. A prosthetic bone implant comprising a cortical portion having    two opposite sides, and a cancellous portion integrally disposed in    said cortical portion and being exposed through said two opposite    sides, wherein said cortical portion comprises a hardened calcium    phosphate cement has a porosity of less than 40% in volume, and said    cancellous portion comprises a porous hardened calcium phosphate    cement having a porosity greater than 20% in volume, and greater    than that of said cortical portion.-   2. The implant according to Item 1, wherein the cortical portion is    in the form of a hollow disk, and the cancellous portion is in the    form of a column surrounded by the hollow disk.-   3. The implant according to Item 2 further comprising a transitional    portion between said column and said hollow disk surrounding said    central cylinder, which has properties range from those of said    cancellous portion to said cortical portion.-   4. The implant according to Item 1, wherein the cortical portion is    in the form of a disk having one or more longitudinal through holes,    and the cancellous portion is in the form of one or more columns    surrounded by said one or more longitudinal through holes.-   5. The implant according to Item 1, wherein said hardened calcium    phosphate cement of said cortical portion comprises an apatitic    phase as a major phase giving rise to broadened characteristic X-ray    diffraction peaks in comparison with a high-temperature sintered    apatitic phase.-   6. The implant according to Item 5, wherein said broadened    characteristic the X-ray diffraction peaks are at 2-Theta values of    25–27° and 30–35°.-   7. The implant according to Item 1, wherein said hardened calcium    phosphate cement of said cortical portion is prepared without a high    temperature sintering.-   8. The implant according to Item 1, wherein said hardened calcium    phosphate cement of said cortical portion comprises an apatitic    phase as a major phase having a Ca/P molar ratio of 1.5–2.0.-   9. The implant according to Item 1, wherein said hardened calcium    phosphate cement of said cancellous portion comprises an apatitic    phase as a major phase giving rise to broadened characteristic X-ray    diffraction peaks in comparison with a high-temperature sintered    apatitic phase.-   10. The implant according to Item 9, wherein said broadened    characteristic the X-ray diffraction peaks are at 2-Theta values of    25–27° and 30–35°.-   11. The implant according to Item 1, wherein said hardened calcium    phosphate cement of said cancellous portion is prepared without a    high temperature sintering.-   12. The implant according to Item 1, wherein said hardened calcium    phosphate cement of said cancellous portion comprises an apatitic    phase as a major phase having a Ca/P molar ratio of 1.5–2.0.-   13. The implant according to Item 1, wherein said cortical portion    comprises 10–90% in volume of said implant.-   14. The implant according to Item 1, wherein said cortical portion    has a porosity of less than 30% in volume.-   15. The implant according to Item 1, wherein said cancellous portion    has a porosity greater than 40–90% in volume.-   16. A method for preparing a prosthetic bone implant comprising a    cortical portion having two opposite sides, and a cancellous portion    integrally disposed in said cortical portion and being exposed    through said two opposite sides, said method comprises the following    steps:    -   a) preparing a first paste comprising a first calcium phosphate        cement and a first setting liquid;    -   b) preparing a second paste comprising a second calcium        phosphate cement, a pore-forming powder and a second setting        liquid;    -   c) i) preparing a shaped article in a mold having two or more        cells separated by one more partition walls comprising        introducing said first paste and said second paste into said two        or more cells separately, and removing said one or more        partition walls from said mold, so that said second paste in the        form of a single column or two or more isolated columns is        integrally disposed in the first paste in said mold; or ii)        preparing a shaped article comprising introducing one of said        first paste and said second paste into a first mold to form an        intermediate in said first mold, placing said intermediate into        a second mold after a hardening reaction thereof undergoes at        least partially, and introducing another one of said first paste        ad said second paste into said second mold, so that said second        paste as a single column or as two or more isolated columns is        integrally disposed in the first paste in said second mold;    -   d) immersing the resulting shaped article from step c) in an        immersing liquid for a first period of time so that said        pore-forming powder is dissolved in the immersing liquid,        creating pores in said single column or said two or more        isolated columns; and    -   e) removing the immersed shaped article from said immersing        liquid.-   17. The method according to Item 16 further comprising    -   f) drying the immersed shaped article.-   18. The method according to Item 16, wherein said pore-forming    powder is selected from the group consisting of LiCl, KCl, NaCl,    MgCl₂, CaCl₂, NaIO₃, KI, Na₃PO₄, K₃PO₄, Na₂CO₃, amino acid-sodium    salt, amino acid-potassium salt, glucose, polysaccharide, fatty    acid-sodium salt, fatty acid-potassium salt, potassium bitartrate    (KHC₄H₄O₆), potassium carbonate, potassium gluconate (KC₆H₁₁O₇),    potassium-sodium tartrate (KNaC₄H₄O₆.4H₂O), potassium sulfate    (K₂SO₄), sodium sulfate, and sodium lactate.-   19. The method according to Item 16, wherein said first calcium    phosphate cement comprises at least one Ca source and at least one P    source, or at least one calcium phosphate source; and said second    calcium phosphate cement comprises at least one Ca source and at    least one P source, or at least one calcium phosphate source.-   20. The method according to Item 19, wherein said first calcium    phosphate cement comprises at least one calcium phosphate source,    and said second calcium phosphate cement comprises at least one    calcium phosphate source.-   21. The method according to Item 20, wherein said calcium phosphate    source is selected from the group consisting of alpha-tricalcium    phosphate (α-TCP), beta-tricalcium phosphate (β-TCP), tetracalcium    phosphate (TTCP), monocalcium phosphate monohydrate (MCPM),    monocalcium phosphate anhydrous (MCPA), dicalcium phosphate    dihydrate (DCPD), dicalcium phosphate anhydrous (DCPA), octacalcium    phosphate (OCP), calcium dihydrogen phosphate, calcium dihydrogen    phosphate hydrate, acid calcium pyrophosphate, anhydrous calcium    hydrogen phosphate, calcium hydrogen phosphate hydrate, calcium    pyrophosphate, calcium triphosphate, calcium phosphate tribasic,    calcium polyphosphate, calcium metaphosphate, anhydrous tricalcium    phosphate, tricalcium phosphate hydrate, and amorphous calcium    phosphate.-   22. The method according to Item 21, wherein said first calcium    phosphate cement and said second calcium phosphate cement are    identical.-   23. The method according to Item 22, wherein said first calcium    phosphate cement and said second calcium phosphate cement are    tetracalcium phosphate.-   24. The method according to Item 16, wherein the first setting    liquid and the second setting liquid independently are an acidic    solution, a basic solution, or a substantially pure water.-   25. The method according to Item 24, wherein said acidic solution is    selected from the group consisting of nitric acid (HNO₃),    hydrochloric acid (HCl), phosphoric acid (H₃PO₄), carbonic acid    (H₂CO₃), sodium dihydrogen phosphate (NaH₂PO₄), sodium dihydrogen    phosphate monohydrate (NaH₂PO₄.H₂O), sodium dihydrogen phosphate    dihydrate, sodium dihydrogen phosphate dehydrate, potassium    dihydrogen phosphate (KH₂PO₄), ammonium dihydrogen.phosphate    (NH₄H₂PO₄), malic acid, acetic acid, lactic acid, citric acid,    malonic acid, succinic acid, glutaric acid, tartaric acid, oxalic    acid and their mixture.-   26. The method according to Item 22, wherein said basic solution is    selected from the group consisting of ammonia, ammonium hydroxide,    alkali metal hydroxide, alkali earth hydroxide, disodium hydrogen    phosphate (Na₂HPO₄), disodium hydrogen phosphate dodecahydrate,    disodium hydrogen phosphate heptahydrate, sodium phosphate    dodecahydrate (Na₃PO₄.12H₂O), dipotassium hydrogen phosphate    (K₂HPO₄), potassium hydrogen phosphate trihydrate (K₂HPO₄.3H₂O),    potassium phosphate tribasic (K₃PO₄), diammonium hydrogen phosphate    ((NH₄)₂HPO₄), ammonium phosphate trihydrate ((NH₄)₃PO₄.3H₂O), sodium    hydrogen carbonate (NaHCO₃), sodium carbonate Na₂CO₃, and their    mixture.-   27. The method according to Item 16, wherein step c-i) further    comprises allowing said first paste and said second paste undergoing    a hardening reaction in said mold.-   28. The method according to Item 16, wherein step c-i) further    comprises pressurizing said first paste and said second paste in    said mold after removing said one or more partition walls from said    mold to remove a portion of liquid from said first paste and said    second paste, so that a liquid/powder ratio of said first paste and    of said second paste decreases; and allowing said first paste and    second paste undergoing a hardening reaction in said mold.-   29. The method according to Item 16, wherein step c-ii) further    comprises allowing said intermediate undergoing a hardening reaction    in said first mold, and allowing said another one of said first    paste and said second paste undergoing a hardening reaction in said    second mold.-   30. The method according to Item 16, wherein step c-ii) further    comprises pressurizing said one of said first paste and said second    paste in said first mold to remove a portion of liquid therefrom    before the hardening reaction of said intermediate is completed;    allowing said intermediate undergoing a hardening reaction in said    first mold; pressuring said another one of said first paste and said    second paste in said second mold, so that a liquid/powder ratio of    said another one of said first paste and of said second paste    decreases; and allowing said another one of said first paste and    second paste undergoing a hardening reaction in said second mold.-   31. The method according to Item 28, wherein said pressuring is    about 1 to 500 MPa.-   32. The method according to Item 30, wherein said pressuring is    about 1 to 500 MPa.-   33. The method according to Item 16, wherein the immersing liquid is    an acidic aqueous solution, a basic aqueous solution, a    physiological solution, an organic solvent, or a substantially pure    water.-   34. The method according to Item 33, wherein the immersing liquid    comprises at least one of Ca and P sources.-   35. The method according to Item 33, wherein the immersing liquid is    a Hanks' solution, a HCl aqueous solution or an aqueous solution of    (NH₄)₂HPO₄.-   36. The method according to Item 16, wherein the immersing in    step d) is carried out for a period longer than 10 minutes.-   37. The method according to Item 16, wherein the immersing in    step d) is carried out for a period longer than 1 day.-   38. The method according to Item 16, wherein the immersing in    step d) is carried out at a temperature of about 10 and 90° C.-   39. The method according to Item 38, wherein the immersing in    step d) is carried out at room temperature.-   40. The method according Item 17 further comprising cleaning said    immersed shaped article before said drying; and heating the    resulting dried shaped article at a temperature between 50 and 500°    C.

Four different designs of prosthetic bone implants constructed accordingto the present invention are shown in FIGS. 1 a to 1 d. In FIG. 1 a, theprosthetic bone implant of the present invention has a dense corticalportion D1 in the tubular form and a porous cancellous portion P1 formedin the central through hole of the tubular cortical portion D1. Both thedense cortical portion D1 and the porous cancellous portion P1 are madeof a hardened calcium phosphate cement having an apatitic phase as amajor phase. In FIG. 1 b, the prosthetic bone implant of the presentinvention has a dense cortical portion D1 in the tubular form; acylindrical porous cancellous portion P1 in the center of the tubularcortical portion D1; and an annular transitional portion P2 connectingthe tubular cortical portion D1 and the cylindrical cancellous portionP1. The transitional portion P2 is made of a hardened calcium phosphatecement having an apatitic phase as a major phase, and a porositygradient increasing from the lower porosity of the cylindricalcancellous portion P1 to the higher porosity of the tubular corticalportion D1, which may be formed in-situ during molding of two differenttwo different CPC pastes, one of them having an additional pore-formingpowder for forming the cylindrical cancellous portion P1, and anotherone being a regular CPC powder for forming the dense cortical portionD1. The porous cancellous portion P1 may be in the forms of isolatedcolumns surrounded by the dense cortical portion D1 as shown in FIGS. 1c and 1 d. Other designs are also possible in addition to those shown inFIGS. 1 a to 1 d.

A suitable method for preparing the prosthetic bone implant of thepresent invention includes placing a tubular partition wall 10 in ahollow cylindrical mold 20, as shown in FIG. 2 a; pouring a first pastecomprising a calcium phosphate cement and a setting liquid in theannular cell and a second paste comprising the calcium phosphate cement,a pore-forming powder and the setting liquid in the central cell, asshown in FIG. 2 b; removing the partition wall and pressing the CPCpastes before hardening, as shown in FIG. 2 c, wherein a portion of thesetting liquid is removed from the gap between the mold 20 and the press30 and/or holes (not shown in the drawing) provided on the press 30. TheCPC paste will undergo a hardening reaction to convert into apatiticphase. The hardened disk is removed from the mold and is subjected tosurface finishing to expose the central portion hardened from the secondpaste, as shown in FIG. 2 d, followed by immersing in a bath of animmersing liquid as shown in FIG. 2 e, where the pore-forming powder isdissolved in the immersing liquid while the hardened CPC thereof gainingcompressive strength. The immersing may last from 10 minutes to severaldays. The composite disk so formed is washed with water after beingremoved from the bath, and dried and heated in an oven to obtain theprosthetic bone implant as shown in FIG. 2 f. The heating is conductedat a temperature between 50 and 500° C. for a period of several hours toseveral days, which enhance the compressive strength of the corticalportion of the prosthetic bone implant.

An alternative method for preparing the prosthetic bone implant of thepresent invention from the same raw materials includes pouring thesecond paste in a first mold, pressing the second paste to remove aportion of the setting liquid from the second paste before the hardeningreaction is completed, so that the liquid/powder ratio in the secondpaste decreases, and allowing the hardening reaction undergo in the moldfor a period of time, e.g. 15 minutes starting from the mixing of theCPC powder, the pore-forming powder and the setting liquid, to obtain acylindrical block having a diameter of 7 mm. Then, the cylindrical blockis removed from the first mold, and placed in the center of a secondmold having a diameter of 10 mm. The first paste is poured into theannular space in the second mold, and a press having a dimensioncorresponding to the annular shape is used to pressure the first pasteto remove a portion of the setting liquid from the first paste beforethe hardening reaction is completed, so that the liquid/powder ratio inthe first paste decreases. Again, the first paste will undergo ahardening reaction to convert into apatitic phase. The hardened cylinderhaving a diameter of 10 mm is removed from the second mold, followed byimmersing in an immersing liquid, where the pore-forming powdercontained in the second paste is dissolved in the immersing liquid whilethe hardened CPC thereof gaining compressive strength, to obtain theprosthetic bone implant of the present invention, as shown in FIGS. 3 aand 3 b. It is apparently to people skilled in the art that theprosthetic bone implant shown in FIGS. 3 a and 3 b can also be preparedby changing the sequence of the molding of the first paste and thesecond paste with modifications to the second mold used in thisalternative method.

The following examples are intended to demonstrate the invention morefully without acting as a limitation upon its scope, since numerousmodifications and variations will be apparent to those skilled in thisart.

PREPARATIVE EXAMPLE 1 Preparation of TTCP Powder

A Ca₄(PO₄)₂O (TTCP) powder was prepared by mixing Ca₂P₂O₇ powder withCaCO₃ powder uniformly in ethanol for 24 hours followed by heating todry. The mixing ratio of Ca₂P₂O₇ powder to CaCO₃ powder was 1:1.27(weight ratio) and the powder mixture was heated to 1400° C. to allowtwo powders to react to form TTCP.

PREPARATIVE EXAMPLE 2 Preparation of Conventional TTCP/DCPA-Based CPCPowder (Abbreviated as C-CPC)

The resulting TTCP powder from PREPARATIVE EXAMPLE 1 was sieved andblended with dried CaHPO₄ (DCPA) powder in a ball mill for 12 hours. Theblending ratio of the TTCP powder to the DCPA powder was 1:1 (molarratio) to obtain the conventional CPC powder. Particles of this C-CPCpowder have no whisker on the surfaces thereof.

PREPARATIVE EXAMPLE 3 Preparation of Non-Dispersive TTCP/DCPA-Based CPCPowder (Abbreviated as ND-CPC)

The TTCP powder prepared according to the method of PREPARATIVE EXAMPLE1 was sieved and blended with dried CaHPO₄ (DCPA) powder in a ball millfor 12 hours. The blending ratio of the TTCP powder to the DCPA powderwas 1:1 (molar ratio). The resultant powder mixture was added to a 25 mMdiluted solution of phosphate to obtain a powder/solution mixture havinga concentration of 3 g powder mixture per 1 ml solution while stirring.The resulting powder/solution mixture was formed into pellets, and thepellets were heated in an oven at 50° C. for 10 minutes. The pelletswere then uniformly ground in a mechanical mill for 20 minutes to obtainthe non-dispersive TTCP/DCPA-based CPC powder (ND-CPC). The particles ofthis ND-CPC powder have whisker on the surfaces thereof.

Dense blocks

EXAMPLE 1 Effect of Immersion Time on Compressive Strength of CPC Block

To a setting solution of IM phosphoric acid solution (pH=5.89) theND-CPC powder from PREPARATIVE EXAMPLE 3 was added in a liquid/powderratio (L/P ratio) of 0.4, i.e. 4 ml liquid/10 g powder, while stirring.The resulting paste was filled into a cylindrical steel mold having alength of 12 mm and a diameter of 6 mm, and was compressed with agradually increased pressure until a maximum pressure was reached. Themaximum pressure was maintained for one minute, and then the compressedCPC block was removed from the mold. At the 15^(th) minute following themixing of the liquid and powder, the compressed CPC block was immersedin a Hanks' solution for 1 day, 4 days, and 16 days. Each test group ofthe three different periods of immersion time has five specimens, thecompressive strength of which was measured by using a AGS-500Dmechanical tester (Shimadzu Co., Ltd., Kyoto, Japan) immediatelyfollowing the removal thereof from the Hanks' solution without drying.The CPC paste in the mold was compressed with a maximum pressure of166.6 MPa, and in the course of the compression the compression speedswere about 5 mm/min during 0˜104.1 MPa; 3 mm/min during 104.1˜138.8 MPa;1 mm/min during 138.8˜159.6 MPa: and 0.5 mm/min during 159.6˜166.6 MPa.The measured wet specimen compressive strength is listed Table 1.

TABLE 1 Compressive Immersion time (Day) strength (MPa) Standarddeviation (MPa) No immersion 37.3* 0.6 1 day 149.2 12.9 4 days 122.7 6.716 days 116.4 7.7 *This value was measured before the compressed CPCblocks were immersed in the Hanks' solution, and it was substantiallythe same for the compressed CPC blocks not immersed in the Hanks'solution measured a few days after the preparation.

It can seen from Table 1 that the compressive strength of the compressedCPC blocks is increased remarkably after one-day immersion in comparisonwith the non-immersed block, and declines a little for a longerimmersion time.

EXAMPLE 2 Effect of Whiskers on Compressive Strength of TTCP/DCPA-BasedCPC Block

The procedures of EXAMPLE 1 were repeated by using the C-CPC powderprepared in PREPARATIVE EXAMPLE 2 and the ND-CPC powder prepared inPREPARATIVE EXAMPLE 3. The maximum pressure used to compress the CPCpaste in the mold in this example was 156.2 MPa. The results for one-dayimmersion time are listed in Table 2.

TABLE 2 Compressive Standard CPC powder strength (MPa) deviation (MPa)C-CPC (no whisker) 62.3 5.0 ND-CPC (with whisker) 138.0 8.2

It can be seen from Table 2 that the compressive strength, 62.3 MPa, ofthe immersed compressed CPC block prepared from the conventional CPCpowder (no whisker) is about 1.7 times of that (37.3 MPa) of thenon-immersed compressed CPC block in Table 1, and the compressivestrength, 138.0 MPa, of the immersed compressed CPC block prepared fromthe non-dispersive CPC powder (with whisker) is about 3.7 times of thatof the non-immersed compressed CPC block in Table 1

EXAMPLE 3 Effect of Whiskers on Compressive Strength of TTCP-Based CPCBlock

Ca₄(PO₄)₂O (TTCP) powder as synthesized in PREPARATIVE EXAMPLE 1 wassieved with a #325 mesh. The sieved powder has an average particle sizeof about 10 μm. To the TTCP powder HCl aqueous solution (pH=0.8) wasadded according to the ratio of 1 g TTCP/13 ml solution. The TTCP powderwas immersed in the HCl aqueous solution for 12 hours, filtered rapidlyand washed with deionized water, and filtered rapidly with a vacuum pumpagain. The resulting powder cake was dried in an oven at 50° C. Thedried powder was divided into halves, ground for 20 minutes and 120minutes separately, and combined to obtain the non-dispersive TTCP-basedCPC powder, the particles of which have whisker on the surfaces thereof.A setting solution of diammonium hydrogen phosphate was prepared bydissolving 20 g of diammonium hydrogen phosphate, (NH₄)₂HPO₄, in 40 mldeionized water. The procedures in EXAMPLE 1 were used to obtain the wetspecimen compressive strength for one-day immersion time, wherein themaximum pressure to compress the CPC paste in the mold was 156.2 MPa.The results are shown in Table 3.

TABLE 3 Compressive Standard CPC powder strength (MPa) deviation (MPa)TTCP (no whisker) 79.6 8.8 TTCP (with whisker) 100 4.2

The trend same as the TTCP/DCPA-based CPC powder in Table 2 of EXAMPLE 2can be observed in Table 3.

EXAMPLE 4 Effect of Molding Pressure on Compressive Strength of ND-CPCBlock (in Low Pressure Regime: 0.09˜3.5 MPa)

The procedures of EXAMPLE 1 were repeated except that the maximumpressure used to compress the CPC paste in the mold was changed from166.6 MPa to the values listed in Table 4. The period of immersion wasone day. The results are listed in Table 4.

TABLE 4 Pressure for compressing the CPC paste in mold CompressiveStandard (MPa) strength (MPa) deviation (MPa) 0.09 12.3 2.0 0.35 16.02.3 0.7 20.7 2.5 1.4 26.4 1.4 3.5 35.2 3.7

The data in Table 4 indicate that the compressive strength of the CPCblock increases as the pressure used to compress the CPC paste in themold increases.

EXAMPLE 5 Effect of Reducing Liquid/Powder Ratio During Compression ofthe CPC Paste in the Mold on Compressive Strength of ND-CPC Block

The procedures of EXAMPLE 1 were repeated except that the maximumpressure used to compress the CPC paste in the mold was changed from166.6 MPa to the values listed in Table 5. The liquid leaked from themold during compression was measured, and the liquid/powder ratio wasre-calculated as shown in Table 5. The period of immersion was one day.The results are listed in Table 5.

TABLE 5 Pressure for compressing the L/P ratio (after CompressiveStandard CPC paste in a portion of strength deviation mold (MPa) liquidremoved) (MPa) (MPa) 1.4 0.25 26.4 1.4 34.7 0.185 75.3 3.9 69.4 0.172100.4 6.8 156.2 0.161 138.0 8.2 166.6 0.141 149.2 12.9

The data in Table 5 show that the compressive strength of the CPC blockincreases as the liquid/powder ratio decreases during molding.

EXAMPLE 6 Effect of Post-Heat Treatment on Compressive Strength of CPCBlock

The procedures of EXAMPLE 1 were repeated. The period of immersion wasone day. The CPC blocks after removing from the Hanks' solution weresubjected to post-heat treatments: 1) 50° C. for one day; and 2) 400° C.for two hours with a heating rate of 10° C. per minute. The results arelisted in Table 6.

TABLE 6 Compressive Standard strength (MPa) deviation (Mpa) No post-heattreatment 149.2 12.9 50° C., one day 219.4 16.0 400° C., two hours 256.716.2

It can be seen from Table 6 that the post-heat treatment enhances thecompressive strength of the CPC block.

Porous Blocks

EXAMPLE 7 Effect of KCl Content and Immersion Time on CompressiveStrength of Porous CPC Block

To a setting solution of IM phosphoric acid solution (pH=5.89) theND-CPC powder from PREPARATIVE EXAMPLE 3 was added in a liquid/powderratio (L/P ratio) of 0.4, i.e. 4 ml liquid/10 g powder, while stirring.KCl powder in a predetermined amount was mixed to the resulting mixtureby stirring intensively. The resulting paste was filled into acylindrical steel mold having a length of 12 mm and a diameter of 6 mm,and was compressed with a gradually increased pressure until a maximumpressure of 3.5 MPa was reached. The maximum pressure was maintained forone minute, and then the compressed CPC block was removed from the mold.At the 15^(th) minute following the mixing of the liquid and powders,the compressed CPC block was immersed in a deionized water at 37° C. for4 days, 8 days, and 16 days. The compressive strength of the specimensof the three different periods of immersion time was measured by using aAGS-500D mechanical tester (Shimadzu Co., Ltd., Kyoto, Japan) after thespecimens were dry. The measured dry specimen compressive strength islisted Table 7.

TABLE 7 Dry compressive strength (MPa) Immersion time (Day) KCl/CPCratio by weight 4 days 8 days 16 days 1 7.0 5.4 6.6 1.5 3.9 2.7 4.3 21.3 2.3 2.6

It can seen from Table 7 that the dry compressive strength of the porousCPC blocks decreases as the KCl/CPC ratio by weight increases.

EXAMPLE 8 Porosity and Compressive Strength of Porous CPC BlocksPrepared From Different Pore-Forming Powders

The procedures of EXAMPLE 7 were repeated by using sugar, KI,C₁₇H₃₃COONa and C₁₃H₂₇COOH instead of KCl. The immersion time was 14days in deionized water. In the cases where the C₁₇H₃₃COONa andC₁₃H₂₇COOH were used, the CPC blocks were further immersed in ethanolfor additional four days. The conditions and the results are listed inTable 8.

TABLE 8 Pore-forming powder S^(a)) C.S. (MPa)^(b)) Porosity (vol %)^(c))Sugar 1 4.1 58.4 KI 2 4.3 62.2 KI 3 1.7 75.5 C17H33COONa 1 8.0 56.0C13H27COOH 2 5.9 60.1 ^(a))S = Pore-forming powder/CPC by volume.^(b))C.S. = dry compressive strength (hereinafter abbreviated as C.S.).^(c))Porosity: Porosity (vol %) was measured by Archimedes' method, andcalculated as in ASTM C830.

It can be seen from Table 8 that various powders which are soluble inwater can be used in the preparation of a porous CPC block according tothe method of the present invention.

Dual-Functional Block

EXAMPLE 9

To a setting solution of IM phosphoric acid solution (pH=5.89) theND-CPC powder from PREPARATIVE EXAMPLE 3 was added in a liquid/powderratio (L/P ratio) of 0.4, i.e. 4 ml liquid/10 g powder, while stirring.KCl powder in a ratio of KCl powder/CPC by volume of 2 was mixed to theresulting mixture by stirring intensively. The resulting paste wasfilled into a cylindrical steel mold having a length of 12 mm and adiameter of 7 mm, and was compressed with a gradually increased pressureuntil a maximum pressure of 3.5 MPa was reached. The maximum pressurewas maintained for one minute, and then the compressed CPC block wasremoved from the mold at the 15^(th) minute following the mixing of theliquid and powders.

The resulting cylinder having a diameter of 7 mm was placed in anothercylindrical steel mold having a diameter of 10 mm. To a setting solutionof IM phosphoric acid solution (pH=5.89) the ND-CPC powder fromPREPARATIVE EXAMPLE 3 was added in a liquid/powder ratio (L/P ratio) of0.4, i.e. 4 ml liquid/10 g powder, while stirring. The resulting pastewas filled into the gap between said cylinder and said another mold, andwas compressed with a gradually increased pressure until a maximumpressure of 50 MPa was reached. The maximum pressure was maintained forone minute. At the 15^(th) minute following the mixing of the liquid andND-CPC powder, the CPC/KCl composite block was immersed in a deionizedwater at 37° C. for 4 days. KCl powder was dissolved in the deionizedwater, and a dual-functional CPC block having a porous CPC cylindersurround by a dense CPC annular block was obtained.

The compressive strength of the specimen was measured by using aAGS-500D mechanical tester (Shimadzu Co., Ltd., Kyoto, Japan) after thespecimens were dry. The measured dry specimen compressive strength is68.8 MPa.

The porosities of the porous CPC cylinder and the dense CPC annularblock were measured by Archimedes' method, and calculated as in ASTMC830, after the dual-functional CPC block was broken intentionally, andthe results are 74% and 30%, respectively.

X-ray diffraction pattern of the powder obtained by grinding thedual-functional CPC block shows broadened characteristic X-raydiffraction peaks of apatite at 2θ=25–27° and 2θ=20–35° with a scanningrange of 2θ of 20–40° and a scanning rate of 1°/min. The resultsindicate that the powder is a mixture of apatite and TTCP with apatiteas a major portion.

1. A method of forming a prosthetic bone implant comprising: adding aporous component paste to one or more first molds, wherein the porouscomponent paste comprises at least one calcium phosphate cement combinedwith at least one pore forming agent and at least one setting agent,wherein the first molds are disposed in a second mold; adding a loadbearing component paste to the second mold; removing one or more of thefirst molds; forming a hardened calcium phosphate article, the hardenedcalcium phosphate article comprising a load bearing component at leastpartially surrounding one or more porous components; immersing thehardened calcium phosphate article in one or more immersing fluids for apredetermined amount of time; and forming the prosthetic bone implant,wherein the prosthetic bone implant comprises the immersed hardenedcalcium phosphate article.
 2. The method of claim 1, wherein one or moreporous components are substantially surrounded by the load bearingcomponent.
 3. The method of claim 1, wherein immersion of the hardenedcalcium phosphate article is carried out at a temperature of from about10° C. to about 90° C.
 4. The method of claim 1, wherein at least oneimmersing liquid comprises at least one source of calcium and least onesource of phosphate.
 5. The method of claim 1, wherein at least oneimmersing liquid comprises Hank's solution.
 6. The method of claim 1,wherein at least one immersing liquid comprises substantially purewater.
 7. The method of claim 1, wherein the hardened calcium phosphatearticle is immersed in at least one immersing liquid for a time periodsufficient to remove at least a portion of the pore forming agent fromthe hardened calcium phosphate article.
 8. The method of claim 1,wherein the hardened calcium phosphate article is immersed in at leastone immersing liquid for at least 10 minutes.
 9. The method of claim 1,wherein the hardened calcium phosphate article is immersed in at leastimmersing liquid for at least 24 hours.
 10. The method of claim 1,wherein the pore-froming agent comprises an inorganic salt.
 11. Themethod of claim 1, wherein the pore-froming agent comprises an organicsalt.
 12. The method of claim 1, wherein the porous component pastecomprises at least one calcium phosphate source, and the load bearingcomponent paste comprises at least one calcium phosphate source.
 13. Themethod of claim 12, wherein the calcium phosphate source comprisesalpha-tricalcium phosphate (α-TCP), beta-tricalcium phosphate (β-TCP),tetracalcium phosphate (TTCP), monocalcium phosphate monohydrate (MCPM),monocalcium phosphate anhydrous (MCPA), dicalcium phosphate dihydrate(DCPD), dicalcium phosphate anhydrous (DCPA), octacalcium phosphate(OCP), calcium dihydrogen phosphate, calcium dihydrogen phosphatehydrate, acid calcium pyrophosphate, anhydrous calcium hydrogenphosphate, calcium hydrogen phosphate hydrate, calcium pyrophosphate,calcium triphosphate, calcium phosphate tribasic, calcium polyphosphate,calcium metaphosphate, anhydrous tricalcium phosphate, tricalciumphosphate hydrate, amorphous calcium phosphate or mixtures thereof. 14.The method of claim 12, wherein the calcium phosphate source comprisestetracalcium phosphate, wherein at least a portion of tetracalciumphosphate particles comprises whiskers on the surface of thetetracalcium phosphate particles.
 15. The method of claim 1, wherein atleast one of the setting agents comprises substantially pure water. 16.The method of claim 1, wherein at least one of the setting agentscomprises an acidic solution, and wherein the acidic solution comprisesnitric acid (HNO₃), hydrochloric acid (HCl), phosphoric acid (H₃PO₄),carbonic acid (H₂CO₃), sodium dihydrogen phosphate (NaH₂PO₄), sodiumdihydrogen phosphate monohydrate (NaH₂PO₄.H₂O), sodium dihydrogenphosphate dihydrate, sodium dihydrogen phosphate dehydrate, potassiumdihydrogen phosphate (KH₂PO₄), ammonium dihydrogen.phosphate (NH₄H₂PO₄),malic acid, acetic acid, lactic acid, citric acid, malonic acid,succinic acid, glutaric acid, tartaric acid, oxalic acid or mixturesthereof.
 17. The method of claim 1, wherein at least one of the settingagents comprises a basic solution, and wherein the basic solutioncomprises ammonia, ammonium hydroxide, alkali metal hydroxide, alkaliearth hydroxide, disodium hydrogen phosphate (Na₂HPO₄), disodiumhydrogen phosphate dodecahydrate, disodium hydrogen phosphateheptahydrate, sodium phosphate dodecahydrate (Na₃PO₄.12H₂O), dipotassiumhydrogen phosphate (K₂HPO₄), potassium hydrogen phosphate trihydrate(K₂HPO₄.3H₂O), potassium phosphate tribasic (K₃PO₄), diammonium hydrogenphosphate ((NH₄)₂HPO₄), ammonium phosphate trihydrate ((NH₄)₃PO₄.3H₂O),sodium hydrogen carbonate (NaHCO₃), sodium carbonate Na₂CO₃, or mixturesthereof.
 18. The method of claim 1, further comprising applying a modingpressure to at least one of the pastes.
 19. The method of claim 18,wherein the molding pressure is in a range from about 1 MPa to about 500MPa.
 20. The method of claim 1, further comprising subjecting thehardened calcium phosphate article to one or more heat treatments,wherein the temperature of the heat treatments is from about 50° C. toabout 500° C.